神经酰胺类鞘脂的绿色生物制造

鲁锦畅; 武耀康; 吕雪芹; 刘龙; 陈坚; 刘延峰

doi:10.12211/2096-8280.2024-059

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神经酰胺类鞘脂的绿色生物制造

特约评述 | 更新时间：2025-05-20

- 神经酰胺类鞘脂的绿色生物制造
- Green biomanufacturing of ceramide sphingolipids
- 合成生物学 2025年6卷第2期页码：422-444
- 作者机构：
  
  1.江南大学生物工程学院，糖化学与生物技术教育部重点实验室，江苏无锡 214112
  2.江南大学未来食品科学中心，江苏无锡 214112
- 作者简介：
  
  [ "鲁锦畅（1999—），女，博士研究生。研究方向为微生物代谢工程。E-mail：7230201010@stu.jiangnan.edu.cn" ]
  [ "刘延峰（1987—），男，博士，研究员。研究方向为微生物代谢工程。E-mail：yanfengliu@jiangnan.edu.cn" ]
- 基金信息：
  
  国家自然科学基金(32222069)
- DOI：10.12211/2096-8280.2024-059
  中图分类号： Q819
- 收稿：2024-08-01，
  
  修回：2024-10-11，
  
  纸质出版：2025-04-30
- 稿件说明：
移动端阅览
鲁锦畅，武耀康，吕雪芹，刘龙，陈坚，刘延峰. 神经酰胺类鞘脂的绿色生物制造［J］. 合成生物学， 2025， 6（2）： 422-444

LU Jinchang， WU Yaokang， LV Xueqin， LIU Long， CHEN Jian， LIU Yanfeng. Green biomanufacturing of ceramide sphingolipids［J］. Synthetic Biology Journal， 2025， 6（2）： 422-444
鲁锦畅，武耀康，吕雪芹，刘龙，陈坚，刘延峰. 神经酰胺类鞘脂的绿色生物制造［J］. 合成生物学， 2025， 6（2）： 422-444 DOI： 10.12211/2096-8280.2024-059.

LU Jinchang， WU Yaokang， LV Xueqin， LIU Long， CHEN Jian， LIU Yanfeng. Green biomanufacturing of ceramide sphingolipids［J］. Synthetic Biology Journal， 2025， 6（2）： 422-444 DOI： 10.12211/2096-8280.2024-059.

摘要

神经酰胺是一种存在于所有真核生物中的多功能生物活性物质，在细胞信号转导、细胞增殖、分化、凋亡和免疫调节中发挥着重要作用。神经酰胺天然存在于皮肤角质层中，起着支持肌肤屏障、保持水分、抗氧化衰老、抗菌抗炎等作用。因此，神经酰胺及其衍生物在化妆品、生物医药、功能食品等领域具有广阔的市场前景。神经酰胺构型存在多个立体中心，化学从头合成难度大，已知市售的天然或类神经酰胺化合物主要是通过传统天然提取法及生物化学相结合的半合成法获得。近年来，利用微生物合成神经酰胺等鞘脂类化合物已有报道，但从头合成效率还处于较低水平，如何实现细胞工厂高效生产神经酰胺具有重大意义。本文从神经酰胺的生理功能和应用出发，系统地综述了神经酰胺类物质的生理效应及功能；阐述了神经酰胺的天然提取方法、神经酰胺及其前体化合物的化学合成方法；并从鞘脂合成途径及关键酶出发介绍，引出途径调控与优化、产物的运输储存与分泌、关键酶的挖掘与表达等改造策略；最后，从神经酰胺合成面临的聚集毒性、高效运输分泌、数字化改造催化元件、基因调控靶点的拓展等方面进行了展望。合成生物学和生物技术的持续进步有助于扩大微生物细胞工厂的生产能力，实现神经酰胺等鞘脂类化合物的可持续绿色生物制造。

Abstract

Ceramide

a fundamental bioactive molecule found ubiquitously in eukaryotic organisms

exerts profound regulatory effect on ce

llular physiology

encompassing critical roles in signaling cascades

cellular proliferation

differentiation

and apoptosis

as well as immunomodulation. In dermatology

ceramides play an indispensable role as constituents of the stratum corneum

the outermost layer of the skin

where they are crucial for maintaining the integrity of the epidermal barrier

regulating moisture retention

combating oxidative stress linked to aging

and exhibiting notable antimicrobial and anti-inflammatory properties. The multifaceted biological functions of ceramides underscore their extensive applications in various industries

including cosmetics

biomedicine

functional food

and animal nutrition

highlighting their significant market potential and therapeutic value. The chemical synthesis of ceramides poses substantial challenges due to the intricate stereochemistry involved

necessitating precise control over synthetic pathways. As a result

current commercial sources predominantly rely on semi-synthetic methods that integrate traditional natural extraction techniques with biochemical transformations of sphingolipid precursors to achieve targeted ceramide structures. Recent advancements in synthetic biology have explored microbial systems for the production of sphingolipids

including ceramides

offering promising avenues for scalable and sustainable synthesis. However

optimizing

de novo

synthesis pathways and their efficiency in microbial cell factories remains a primary research focus. Strategies aimed at enhancing ceramide yield and purity through metabolic engineering and pathway optimization are pivotal for advancing industrial applications. This paper provides a systematic review of the physiological effectiveness and function of ceramides

encompassing their physiological roles and various applications. It begins with an overview of ceramide extraction methods

including both natural extraction techniques and chemical synthesis approaches for ceramides and their precursor compounds. Subsequently

the

review addresses the sphingolipid synthesis pathways and their associated key enzymes

detailing strategies for pathway regulation and optimization

as well as the aspects of product transport

storage

and secretion. Additionally

it explores the identification and expression of key enzymes. The paper concludes by examining future directions in the field

such as addressing aggregation toxicity in ceramide synthesis

enhancing transport and secretion mechanisms

advancing digital modifications of catalytic elements

and expanding gene regulatory target exploration. By synthesizing current knowledge and highlighting avenues for innovation

this review aims to catalyze further research effort toward achieving efficient ceramide production. Ultimately

optimizing ceramide synthesis has the potential to unlock its full potential in various sectors

contributing to its advancement in skincare

therapeutics

and functional materials. The integration of microbial systems is particularly promising for expanding production capabilities while addressing sustainability concerns in ceramide manufacturing. Continued advancements in synthetic biology and biotechnology are expected to revolutionize the landscape of ceramide applications

paving the way for enhanced therapeutic interventions and novel industrial applications in the future.

关键词

Keywords

references

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